Abstract
Mutant mice deficient in hyaluronan (HA) have an epileptic phenotype. HA is one of the major constituents of the brain extracellular matrix. HA has a remarkable hydration capacity, and a lack of HA causes reduced extracellular space (ECS) volume in the brain. Reducing ECS volume can initiate or exacerbate epileptiform activity in many in vitro models of epilepsy. There is both in vitro and in vivo evidence of a positive feedback loop between reduced ECS volume and synchronous neuronal activity. Reduced ECS volume promotes epileptiform activity primarily via enhanced ephaptic interactions and increased extracellular potassium concentration; however, the epileptiform activity in many models, including the brain slices from HA synthase-3 knockout mice, may still require glutamate-mediated synaptic activity. In brain slice epilepsy models, hyperosmotic solution can effectively shrink cells and thus increase ECS volume and block epileptiform activity. However, in vivo, the intravenous administration of hyperosmotic solution shrinks both brain cells and brain ECS volume. Instead, manipulations that increase the synthesis of high-molecular-weight HA or decrease its breakdown may be used in the future to increase brain ECS volume and prevent seizures in patients with epilepsy. The prevention of epileptogenesis is also a future target of HA manipulation. Head trauma, ischemic stroke, and other brain insults that initiate epileptogenesis are known to be associated with an early decrease in high-molecular-weight HA, and preventing that decrease in HA may prevent the epileptogenesis.
Acknowledgments
This work was supported by the National Institutes of Health, National Institute of Neurological Disorders and Stroke grant R01 NS047557.
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Articles in the same Issue
- Frontmatter
- Alzheimer’s disease: as it was in the beginning
- Cognitive impairment in multiple sclerosis – a review of current knowledge and recent research
- The role of ubiquitin proteasomal system and autophagy-lysosome pathway in Alzheimer’s disease
- Brain extracellular space, hyaluronan, and the prevention of epileptic seizures
- Iron in neurodegenerative disorders: being in the wrong place at the wrong time?
- Wearable technology for patients with brain and spinal cord injuries
Articles in the same Issue
- Frontmatter
- Alzheimer’s disease: as it was in the beginning
- Cognitive impairment in multiple sclerosis – a review of current knowledge and recent research
- The role of ubiquitin proteasomal system and autophagy-lysosome pathway in Alzheimer’s disease
- Brain extracellular space, hyaluronan, and the prevention of epileptic seizures
- Iron in neurodegenerative disorders: being in the wrong place at the wrong time?
- Wearable technology for patients with brain and spinal cord injuries